Abstract
Testicular damage is one of the most deleterious effects whenever cisplatin (CIS) is employed in cancer chemotherapy. Oxidative stress has been proven to be involved in CIS induced toxicity. Thus, the current study explored the possible protective effect of L-carnitine (L-CAR) against cisplatin-induced testicular damage in rats. L-carnitine (500 mg/kg/day; i.p.) was injected for 15 days, whereas cisplatin (10 mg/kg; i.p.) was injected as a single dose at the 12th day to induce testicular damage in adult male Sprague-Dawley rats. In the current study, CIS reduced the reproductive organs weight, sperm count, sperm motility and serum testosterone level beside a marked increase in the incidence of sperm abnormalities. In addition, it significantly increased malondialdehyde (MDA) and nitric oxide (NO) along with a marked decrease in testis reduced glutathione (GSH) content and superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities. At the same time, CIS administration resulted in marked elevation in tumor necrosis factor-α (TNF-α) production and nuclear factor-kabba B (NF-κB) expression. These results were confirmed by histopathological examination. Treatment with L-CAR markedly attenuated cisplatin-induced injury by suppression of oxidative/nitrosative stress and inflammation, amendment of antioxidant defenses, as well as improvement of steroidogenesis, spermatogenesis and testicular histological features. This study suggests a novel therapeutic application for L-carnitine as a protective agent against cisplatin-induced testicular toxicity through its promising anti-inflammatory and antioxidant capacities.
Highlights
Cisplatin is a highly effective and commonly used DNA alkylating chemotherapeutic agent for the treatment of diverse types of solid tumors (Amin and Buratovich, 2009)
The relative weights of right and left testis, cauda epididymis, prostate and seminal vesicle were significantly decreased after cisplatin exposure to 82.9%, 85.2%, 76.6%, 73.7% and 80.7 % of the control group; respectively, while all of them were normalized by L-carnitine administration (Table 1)
It seems imperative to search for agents that can protect against testicular toxicity whenever cisplatin chemotherapy is employed
Summary
Cisplatin is a highly effective and commonly used DNA alkylating chemotherapeutic agent for the treatment of diverse types of solid tumors (Amin and Buratovich, 2009). Despite the improvement in quality of life of cancer patients; the use of cisplatin was restricted clinically by its major side effects including testicular toxicity (Fung and Vaughn, 2011; Beytur et al, 2012). Cisplatin was found to produce severe testicular toxicity, characterized by impaired spermatogenesis, sperm DNA damage and sperm chromosomal abnormalities (Fung and Vaughn, 2011; Beytur et al, 2012). The mechanisms underlying cisplatin-induced testicular injury involves disruptions of the redox balance of testicular tissues via an increase in mitochondrial dysfunction, oxidative/nitrosative stress and lipid peroxidation which result in inhibition of protein synthesis and DNA damage (Ahmed et al, 2011; Rezvanfar et al, 2013). Growing evidences revealed that combination therapy of cisplatin with antioxidants can be beneficial to overcome this special reproductive toxicity (Ahmed et al, 2011; Turk et al, 2011; Aldemir et al, 2014; Sherif et al, 2014)
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